The overall goal of this project is to understand the effects of Chinese herbs in the treatment of prostate cancer. Essentially all men with advanced prostate cancer treated with androgen-ablation therapy eventually have the untoward result of the tumor attaining androgen- independent growth. At present, there is no effective treatment for tumors that are hormone refractory. PC SPES, which contains a combination of eight Chinese herbs, has been available on the market as a dietary supplement for men with prostate cancer since 1996. Because this preparation is marked as having 'anti-tumor, anti-viral, and immune stimulating activity and there is limited laboratory evidence for some of these effects, we will evaluate the effects of short-term use of the herbal formulation on PSA, as a tumor marker, and on neuroendocrine and immune markers. Our overall hypothesis is that Chinese herbs, in the form of PC SPES, by modulating neuroendocrine, immune, and anti- oxidant markers, are beneficial in the following specific aims: 1) To evaluate the effects of short term administration of Chinese herbs, as PC- SPES versus estrogen-only, as estradiol. on disease progression in men with prostate cancer who have been androgen deprived and now have increasing serum PSA levels, 2) To determine the effect of these interventions on neuroendocrine, immunologic, and anti-oxidant parameters of prostate cancer, 3) To evaluate change in sexual function and quality of life in men with prostate cancer treated with PC SPES or estradiol, 4) To determine the safety of PC-SPES in men with prostate cancer on hypogonadal signals and symptoms of hypogonadism, thromboembolic events, clotting factors, markers of bone turnover, bone density, and body composition. To accomplish our goals, we propose to examine the efficiency and safety of using Pc-SPES versus estradiol alone in a randomized, placebo, controlled clinical trial enrolling U.S. white and African-American men with hormone refractory prostate cancer. In addition, we intend to develop a parallel study in Chinese men at the Johns Hopkins Singapore Campus in order to expand out opportunities for investigation at that locale and understand the logistics to plan future studies.